SYNTHESIS OF AND VESICLE FORMATION FROM PHOSPHORYLCHOLINE AMPHIPHILES WITH ONE SYMMETRICALLY BRANCHED ALKYL CHAIN

Three phosphorylcholines with symmetrically branched alkyl chains [(CnH2n+1)2 CHOPO3- (CH2)2N(CH3)3+] (la-c) have been synthesized. The synthesis involves three steps: (1) reaction of the alcohol (CnH2n+1)2CHOH, (n = 6, 8, 10) with 2-chloro-1,3,2-dioxaphospholane in the presence of triethylamine; (2) oxidation of the resulting trialkyl phosphite with nitrogen dioxide and (3) ring opening of the cyclic phosphate triester by trimethylamine in acetonitrile. When suspended in water, these amphiphiles all form bilayer vesicles as revealed by electron microscopy and NMR spectroscopy. The vesicles have diameters of 300-1000 angstrom and are stable for more than a week.